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Int J Mol Sci. 2019 Jun 22;20(12). pii: E3055. doi: 10.3390/ijms20123055.

Caffeic Acid Phenethyl Ester Inhibits UV-Induced MMP-1 Expression by Targeting Histone Acetyltransferases in Human Skin.

Author information

1
Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Korea. Shin.Eun-Ju@kfri.re.kr.
2
Division of Bioengineering, Incheon National University, Incheon 22012, Korea. friend9698@naver.com.
3
Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Korea. chkyoung@kfri.re.kr.
4
Division of Bioengineering, Incheon National University, Incheon 22012, Korea. 201921148@inu.ac.kr.
5
Division of Bioengineering, Incheon National University, Incheon 22012, Korea. sbyun@inu.ac.kr.
6
Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Korea. tglim83@kfri.re.kr.

Abstract

Caffeic acid phenethyl ester (CAPE), a naturally occurring bioactive compound, displays anti-inflammatory, anti-carcinogenic, and anti-microbial effects. However, the effect of CAPE on skin photoaging is unknown. Herein, we investigated the inhibitory effect of CAPE against ultraviolet (UV) irradiation-mediated matrix metalloproteinase (MMP)-1 expression and its underlying molecular mechanism. CAPE treatment suppressed UV-induced MMP-1 levels in both human dermal fibroblasts (HDF) and human skin tissues. While CAPE did not display any significant effects against the upstream regulatory pathways of MMP-1, CAPE was capable of reversing UV-mediated epigenetic modifications. CAPE suppressed UV-induced acetyl-histone H3 (Lys9) as well as total lysine acetylation in HDF cells. Similarly, CAPE also attenuated UV-induced lysine acetylations in human skin tissues, suggesting that the CAPE-mediated epigenetic alterations can be recapitulated in ex vivo conditions. CAPE was found to attenuate UV-induced histone acetyltransferase (HAT) activity in HDF. Notably, CAPE was able to directly inhibit the activity of several HATs including p300, CREP-binding protein (CBP), and p300/CBP-associated factor (PCAF), further confirming that CAPE can function as an epigenetic modulator. Thus, our study suggests that CAPE maybe a promising agent for the prevention of skin photoaging via targeting HATs.

KEYWORDS:

MMP-1; caffeic acid phenethyl ester; histone acetylation; histone acetyltransferase; skin aging

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